between 2 and 2.5 for the Dutch 2002 PDV epidemic., Heterogeneities in transmission among hosts can be very important in shaping infectious disease dynamics. In mammals with
strong social ...organization, such heterogeneities are often structured by functional stage: juveniles, subadults and adults.
We investigate the importance of such stage-related heterogeneities in shaping the 2002 phocine distemper virus (PDV) outbreak
in the Dutch Wadden Sea, when more than 40 per cent of the harbour seals were killed. We do this by comparing the statistical
fit of a hierarchy of models with varying transmission complexity: homogeneous versus heterogeneous mixing and density- versus
frequency-dependent transmission. We use the stranding data as a proxy for incidence and use Poisson likelihoods to estimate
the ‘who acquires infection from whom’ (WAIFW) matrix. Statistically, the model with strong heterogeneous mixing and density-dependent
transmission was found to best describe the transmission dynamics. However, patterns of incidence support a model of frequency-dependent
transmission among adults and juveniles. Based on the maximum-likelihood WAIFW matrix estimates, we use the next-generation
formalism to calculate an
SARS-CoV-2 lineage B.1.1.7, a variant that was first detected in the UK in September 2020
, has spread to multiple countries worldwide. Several studies have established that B.1.1.7 is more ...transmissible than pre-existing variants, but have not identified whether it leads to any change in disease severity
. Here we analyse a dataset that links 2,245,263 positive SARS-CoV-2 community tests and 17,452 deaths associated with COVID-19 in England from 1 November 2020 to 14 February 2021. For 1,146,534 (51%) of these tests, the presence or absence of B.1.1.7 can be identified because mutations in this lineage prevent PCR amplification of the spike (S) gene target (known as S gene target failure (SGTF)
). On the basis of 4,945 deaths with known SGTF status, we estimate that the hazard of death associated with SGTF is 55% (95% confidence interval, 39-72%) higher than in cases without SGTF after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55-69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8-1.0%) within 28 days of a positive test in the community. Correcting for misclassification of SGTF and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42-82%) higher than with pre-existing variants. Our analysis suggests that B.1.1.7 is not only more transmissible than pre-existing SARS-CoV-2 variants, but may also cause more severe illness.
We evaluated effectiveness of thermal passenger screening for 2019-nCoV infection at airport exit and entry to inform public health decision-making. In our baseline scenario, we estimated that 46% ...(95% confidence interval: 36 to 58) of infected travellers would not be detected, depending on incubation period, sensitivity of exit and entry screening, and proportion of asymptomatic cases. Airport screening is unlikely to detect a sufficient proportion of 2019-nCoV infected travellers to avoid entry of infected travellers.
The isolation of symptomatic cases and tracing of contacts has been used as an early COVID-19 containment measure in many countries, with additional physical distancing measures also introduced as ...outbreaks have grown. To maintain control of infection while also reducing disruption to populations, there is a need to understand what combination of measures—including novel digital tracing approaches and less intensive physical distancing—might be required to reduce transmission. We aimed to estimate the reduction in transmission under different control measures across settings and how many contacts would be quarantined per day in different strategies for a given level of symptomatic case incidence.
For this mathematical modelling study, we used a model of individual-level transmission stratified by setting (household, work, school, or other) based on BBC Pandemic data from 40 162 UK participants. We simulated the effect of a range of different testing, isolation, tracing, and physical distancing scenarios. Under optimistic but plausible assumptions, we estimated reduction in the effective reproduction number and the number of contacts that would be newly quarantined each day under different strategies.
We estimated that combined isolation and tracing strategies would reduce transmission more than mass testing or self-isolation alone: mean transmission reduction of 2% for mass random testing of 5% of the population each week, 29% for self-isolation alone of symptomatic cases within the household, 35% for self-isolation alone outside the household, 37% for self-isolation plus household quarantine, 64% for self-isolation and household quarantine with the addition of manual contact tracing of all contacts, 57% with the addition of manual tracing of acquaintances only, and 47% with the addition of app-based tracing only. If limits were placed on gatherings outside of home, school, or work, then manual contact tracing of acquaintances alone could have an effect on transmission reduction similar to that of detailed contact tracing. In a scenario where 1000 new symptomatic cases that met the definition to trigger contact tracing occurred per day, we estimated that, in most contact tracing strategies, 15 000–41 000 contacts would be newly quarantined each day.
Consistent with previous modelling studies and country-specific COVID-19 responses to date, our analysis estimated that a high proportion of cases would need to self-isolate and a high proportion of their contacts to be successfully traced to ensure an effective reproduction number lower than 1 in the absence of other measures. If combined with moderate physical distancing measures, self-isolation and contact tracing would be more likely to achieve control of severe acute respiratory syndrome coronavirus 2 transmission.
Wellcome Trust, UK Engineering and Physical Sciences Research Council, European Commission, Royal Society, Medical Research Council.
In December, 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, emerged in Wuhan, China. Since then, the city of Wuhan has taken unprecedented measures in ...response to the outbreak, including extended school and workplace closures. We aimed to estimate the effects of physical distancing measures on the progression of the COVID-19 epidemic, hoping to provide some insights for the rest of the world.
To examine how changes in population mixing have affected outbreak progression in Wuhan, we used synthetic location-specific contact patterns in Wuhan and adapted these in the presence of school closures, extended workplace closures, and a reduction in mixing in the general community. Using these matrices and the latest estimates of the epidemiological parameters of the Wuhan outbreak, we simulated the ongoing trajectory of an outbreak in Wuhan using an age-structured susceptible-exposed-infected-removed (SEIR) model for several physical distancing measures. We fitted the latest estimates of epidemic parameters from a transmission model to data on local and internationally exported cases from Wuhan in an age-structured epidemic framework and investigated the age distribution of cases. We also simulated lifting of the control measures by allowing people to return to work in a phased-in way and looked at the effects of returning to work at different stages of the underlying outbreak (at the beginning of March or April).
Our projections show that physical distancing measures were most effective if the staggered return to work was at the beginning of April; this reduced the median number of infections by more than 92% (IQR 66–97) and 24% (13–90) in mid-2020 and end-2020, respectively. There are benefits to sustaining these measures until April in terms of delaying and reducing the height of the peak, median epidemic size at end-2020, and affording health-care systems more time to expand and respond. However, the modelled effects of physical distancing measures vary by the duration of infectiousness and the role school children have in the epidemic.
Restrictions on activities in Wuhan, if maintained until April, would probably help to delay the epidemic peak. Our projections suggest that premature and sudden lifting of interventions could lead to an earlier secondary peak, which could be flattened by relaxing the interventions gradually. However, there are limitations to our analysis, including large uncertainties around estimates of R0 and the duration of infectiousness.
Bill & Melinda Gates Foundation, National Institute for Health Research, Wellcome Trust, and Health Data Research UK.
To inform Chlamydia trachomatis (CT) infection control, the objectives of the second Slovenian National Survey of Sexual Lifestyles, Attitudes, and Health in 2016-2017 were to estimate the prevalence ...of and identify risk factors for CT infection among sexually experienced 18- to 49-year-olds in Slovenia.
Data were collected from a probability sample of the general population 18 to 49 years old. Respondents were invited to provide a urine specimen for CT testing. Data were analyzed using STATA 15 survey commands to account for stratification and clustering.
Of 1,046 CT test results of sexually experienced respondents included in the analyses, the weighted prevalence of CT infection was 0.5% (95% confidence interval CI: 0.1-1.9) in men and 1.7% (95% CI: 0.9-3.3) in women. The highest prevalence was among women 18 to 24 years old (5.6%; 95% CI: 2.0-14.4). Women 18 to 49 years old with a new sex partner in the last year had higher odds of CT infection (adjusted odds ratio: 8.9, 95% CI: 2.5-31.9).
The introduction of annual opportunistic testing for CT should be considered for sexually active women < 25 years old, and testing should be offered at primary healthcare gynecology clinics to older women reporting a new sex partner during the past year.
Successful control measures have interrupted the local transmission of human infectious diseases such as measles, malaria and polio, and saved and improved billions of lives. Similarly, control ...efforts have massively reduced the incidence of many infectious diseases of animals, such as rabies and rinderpest, with positive benefits for human health and livelihoods across the globe. However, disease elimination has proven an elusive goal, with only one human and one animal pathogen globally eradicated. As elimination targets expand to regional and even global levels, hurdles may emerge within the endgame when infections are circulating at very low levels, turning the last mile of these public health marathons into the longest mile. In this theme issue, we bring together recurring challenges that emerge as we move towards elimination, highlighting the unanticipated consequences of particular ecologies and pathologies of infection, and approaches to their management.
Stage-structured epidemic models provide a way to connect the interacting processes of infection and demography. Reproduction and development can replenish the pool of susceptible hosts, and ...demographic structure leads to heterogeneous transmission and disease risk. Epidemics, in turn, can increase mortality or reduce fertility of the host population. Here we present a framework that integrates both demography and epidemiology in models for stage-structured epidemics. We use the vec-permutation matrix approach to classify individuals jointly by their demographic stage and infection status. We describe demographic and epidemic processes as alternating in time with a periodic matrix model. The application of matrix calculus to this framework allows for the calculation of
and sensitivity analysis.
The past two decades have seen expansion of childhood vaccination programmes in low-income and middle-income countries (LMICs). We quantify the health impact of these programmes by estimating the ...deaths and disability-adjusted life-years (DALYs) averted by vaccination against ten pathogens in 98 LMICs between 2000 and 2030.
16 independent research groups provided model-based disease burden estimates under a range of vaccination coverage scenarios for ten pathogens: hepatitis B virus, Haemophilus influenzae type B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, Streptococcus pneumoniae, rotavirus, rubella, and yellow fever. Using standardised demographic data and vaccine coverage, the impact of vaccination programmes was determined by comparing model estimates from a no-vaccination counterfactual scenario with those from a reported and projected vaccination scenario. We present deaths and DALYs averted between 2000 and 2030 by calendar year and by annual birth cohort.
We estimate that vaccination of the ten selected pathogens will have averted 69 million (95% credible interval 52–88) deaths between 2000 and 2030, of which 37 million (30–48) were averted between 2000 and 2019. From 2000 to 2019, this represents a 45% (36–58) reduction in deaths compared with the counterfactual scenario of no vaccination. Most of this impact is concentrated in a reduction in mortality among children younger than 5 years (57% reduction 52–66), most notably from measles. Over the lifetime of birth cohorts born between 2000 and 2030, we predict that 120 million (93–150) deaths will be averted by vaccination, of which 58 million (39–76) are due to measles vaccination and 38 million (25–52) are due to hepatitis B vaccination. We estimate that increases in vaccine coverage and introductions of additional vaccines will result in a 72% (59–81) reduction in lifetime mortality in the 2019 birth cohort.
Increases in vaccine coverage and the introduction of new vaccines into LMICs have had a major impact in reducing mortality. These public health gains are predicted to increase in coming decades if progress in increasing coverage is sustained.
Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation.
Background:
A novel coronavirus disease (COVID-19) outbreak has now spread to a number of countries worldwide. While sustained transmission chains of human-to-human transmission suggest high basic ...reproduction number
R
0
, variation in the number of secondary transmissions (often characterised by so-called superspreading events) may be large as some countries have observed fewer local transmissions than others.
Methods:
We quantified individual-level variation in COVID-19 transmission by applying a mathematical model to observed outbreak sizes in affected countries. We extracted the number of imported and local cases in the affected countries from the World Health Organization situation report and applied a branching process model where the number of secondary transmissions was assumed to follow a negative-binomial distribution.
Results:
Our model suggested a high degree of individual-level variation in the transmission of COVID-19. Within the current consensus range of
R
0
(2-3), the overdispersion parameter
k
of a negative-binomial distribution was estimated to be around 0.1 (median estimate 0.1; 95% CrI: 0.05-0.2 for R0 = 2.5), suggesting that 80% of secondary transmissions may have been caused by a small fraction of infectious individuals (~10%). A joint estimation yielded likely ranges for
R
0
and
k
(95% CrIs:
R
0
1.4-12;
k
0.04-0.2); however, the upper bound of
R
0
was not well informed by the model and data, which did not notably differ from that of the prior distribution.
Conclusions:
Our finding of a highly-overdispersed offspring distribution highlights a potential benefit to focusing intervention efforts on superspreading. As most infected individuals do not contribute to the expansion of an epidemic, the effective reproduction number could be drastically reduced by preventing relatively rare superspreading events.
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